BETHESDA, Md. - Rheumatoid arthritis patients who failed to respond to methotrexate may have better luck the second time around, a study here suggests.

Action Points

Consider a second course of methotrexate in rheumatoid arthritis patients who did not respond to an initial course of this drug and did not have major toxicity.

Be aware that on the basis of the study a second course of methotrexate may have increased chance of success in patients for whom the dose of the first treatment was 10 mg per week or less.

BETHESDA, Md., Feb. 24 - Rheumatoid arthritis patients who failed to respond to methotrexate may have better luck the second time around, a study here suggested.

More than half of patients for whom the drug didn't work initially responded to a second course, reported Daniel Aletaha, M.D., of the Medical University of Vienna, who is a research fellow at the National Institute of Arthritis and Musculoskeletal and Skin Diseases here, and colleagues in Austria.

Previous studies have shown that the majority of RA patients taking a disease-modifying, antirheumatic drug (DMARD) discontinue within three to five years because of lack of efficacy or adverse events. For these patients, new drug options are often limited, Dr. Aletaha and colleagues said.

The current research, published online today by Arthritis Research & Therapy, includes a retrospective study of patients who had undergone at least one course of DMARD therapy at the Vienna General Hospital and Hietzing Hospital in Vienna between 1989 and 1997 and a prospective study of patients from 1997 to 2004. In all, there were more than 1,400 patients, some in both studies.

Focusing on 79 patients who had a second methotrexate treatment lasting at least one year, the researchers reported:

â€¢ Forty-two (53.2%) had an effective second treatment (P=.022).

â€¢ The second treatment was effective in 23 (45.1%) of the patients who had stopped treatment because of lack of efficacy (P=.022).

â€¢ Sixteen (66.7%) of the patients who had initially stopped treatment because of adverse events had a successful second treatment (P=.033).

â€¢ The second treatment was more than twice as likely to be successful if the methotrexate dose in the first treatment had been low (10 mg per week or less) than if it had been high (greater than 17.5 mg per week; P=.02 for trend).

The average time interval between the first course of methotrexate and the second was two years. During this interim, patients had tried at least one and up to seven DMARDs.

There was no difference in efficacy between first and second treatment for other DMARDs analyzed in the study, which mainly included Azulfidine (sulfasalazine) and Aralen (chloroquine), the investigators reported.

"Reconsidering the use of methotrexate seems to be a rational approach if there was no major toxicity during a previous course of methotrexate," the authors concluded.

"This therapeutic option may be valuable in patients in whom other therapies, especially biologicals, cannot be used or have proven insufficiently effective," they said.

Reviewed by Zalman S. Agus, MD Emeritus Professor at the University of Pennsylvania School of Medicine